Studies On Quality Control Methods For The Manufacturing Process Of Tanreqing Injection

Currently, the big challenges in the traditional Chinese Medicine (TCM) industry are lacking of advanced manufacturing process supervisory techniques to renew the backward quality evaluation methods, so that the quality of TCMs is hard to be improved. For this reason, taking a TCM preparation, Tanreqing injection as the research carrier, this paper accordingly focused on the investigation of rapid analysis method for the quality assessment of TCM raw materials and extracts with near infrared spectroscopy (NIRS), and also the Process quality control methods for the liquid preparation process, by combination of the modern instrument analytical techniques and pharmaceutical analysis information technologies. Ultimately, the process quality control method of TCM was established, and the research findings were used in industrial practice. The main innovation and academic contributions of this dissertation are presented as follows:1. The rapid quality control methods for the TCM materials were established. Firstly, an NIRS method was developed for the authentication of bear bile powder; Secondly, an NIRS method was developed for the growth pattern and geographical origin discrimination and content determination of 4 flavonoids in Radix Scutellariae; Thirdly, an NIRS method was developed for the geographical origin discrimination and content determination of 6 organic acids in Lonicera japonica; Finally, the discrimination method of Fructus Forsythiae from different geographical origin and different harvesting stages was developed, and the proportion of Green forsythia in the raw materials was determined. This research is helpful to the raw material purchase and the quality testing before the raw materials put into production.2. The quality control method based on the NIRS technology for the TCM extracts is researched. An NIRS method was established for the measurement of moisture contents in 5 kinds of TCM extracts, and rapid analysis methods for the determination of UDCA and CDCA in the bear gall powder extracts,6 organic acids in Lonicera japonica extracts, and 12 amino acids in the Cornus Caprae Hircus extracts were also developed.3. The rapid NIRS determination method of the final product was established. A homemade accessory was used for the non-invasive analysis. And with the accessory, several internal control indexes were determined without opening the vials. Generally speaking, the quality of Tanreqing injection is stable, which will make the robust calibration models not easily to be developed. To resolve this issue, more representative samples were prepared, which can increase the representativeness of the calibration set effectively. The calibration transfer method was also researched for the more widely use of the models. This research can reduce the workload of product inspection to a large extent, and the sampling proportion can be increased properly, which will contribute to improve the reliability of determination results.4. Focus studies on the liquid preparation process were done to enhance the process understanding. Firstly, the method of discriminant analysis was established for the total mixing liquid samples with different concentration and pH values. Secondly, A method for rapid quantitative analysis of 4 kinds of Tanreqing injection intermediates was developed.